10 basics of human genetics

Basics Of Human Basics Of Human GeneticsGenetics

ByByProf. Dr. Randa YoussefProf. Dr. Randa Youssef

Kasr El AiniKasr El Aini

Introduction to molecular Introduction to molecular geneticsgenetics

GenomeGenome : the total number of genes : the total number of genes contained in one cell.contained in one cell.

There are 3 billion bp in each human There are 3 billion bp in each human haploid genome.haploid genome.

The genome contains 1 million genes, The genome contains 1 million genes, only 50,000 are functioning.only 50,000 are functioning.

Gene Gene GeneGene : the unit of heredity that occupies a : the unit of heredity that occupies a

specific locus on the chromosome. It is a specific locus on the chromosome. It is a DNA sequence that directs synthesis of a DNA sequence that directs synthesis of a specific polypeptide chain.specific polypeptide chain.

1% has specific function1% has specific functionGenes Genes

Structural regulatory operator Structural regulatory operator

Structural GStructural G: directs synthesis of a specific : directs synthesis of a specific polypeptide chain.polypeptide chain.

Regulatory GRegulatory G: repressor substance : repressor substance secretion.secretion.

Operator GOperator G: switches on structural G: switches on structural G Not all genetic information is stored using the Not all genetic information is stored using the

genetic code. All organisms' DNA contains genetic code. All organisms' DNA contains regulatory sequences, intergenic segments, regulatory sequences, intergenic segments, chromosomal structural areas, and other non-chromosomal structural areas, and other non-coding DNA that can contribute greatly to coding DNA that can contribute greatly to phenotype. phenotype.

Regulation of gene expressionRegulation of gene expression Not all genes are transcribed all the time.Not all genes are transcribed all the time. Controlling mechanisms in the cell Controlling mechanisms in the cell

regulate the flow of enzymes& other regulate the flow of enzymes& other proteins, determining which genes are proteins, determining which genes are turned on. turned on.

Some genes are needed for short periods Some genes are needed for short periods of life cycle, others such as those involved of life cycle, others such as those involved in energy production may be operating all in energy production may be operating all time. time.

AutosomeAutosome : any chromosome that is not a : any chromosome that is not a sex (X or Y) chromosome.sex (X or Y) chromosome.

PseudogenePseudogene : a gene which resemble a : a gene which resemble a known structural gene but is not known structural gene but is not expressed.expressed.

GenotypeGenotype : the genetic constitution of an : the genetic constitution of an organism.organism.

PhenotypePhenotype : the physical appearance of : the physical appearance of an organism that is produced by the an organism that is produced by the interaction of his genes & environment.interaction of his genes & environment.

StructureStructure of DNA of DNA Two polynucleotide Two polynucleotide strands. strands. Two chains run in Two chains run in opposite direction.opposite direction. Sugar-P backbone Sugar-P backbone Bases inside helixBases inside helix Complementary base Complementary base pairing (A=T &C pairing (A=T &C ==

G)G) Strands bonded by Strands bonded by weak hydrogen weak hydrogen

bondsbonds

Nucleotides & Nucleotides & codonscodons

nucleotide= base +sugar nucleotide= base +sugar +phosphate+phosphate

Triplet= sequence of 3 basesTriplet= sequence of 3 basesCodon consists of three Codon consists of three nucleotides, representing a nucleotides, representing a single amino acid.single amino acid.

(4(433)=64 aa, only 20 are present )=64 aa, only 20 are present (different codons for the same (different codons for the same aa)aa)

Coiling of DNACoiling of DNA Primary coiling of the duplex itself.Primary coiling of the duplex itself. 2ry coiling around histone beads 2ry coiling around histone beads

(nucleosome).(nucleosome). 3ry coiling of nucleosomes ( chromatin 3ry coiling of nucleosomes ( chromatin

fibers).fibers). 4ry coiling forming loops.4ry coiling forming loops.

Coiling of DNACoiling of DNA

Gene mutationGene mutation A change in the nucleotide sequence of the A change in the nucleotide sequence of the

DNA.DNA. 1-Silent :1-Silent : Another triplet for the same aaAnother triplet for the same aa intragenicintragenic 2-Hazardous: 2-Hazardous: in coding gene (change in a protein or its aa).in coding gene (change in a protein or its aa). If it occurs in somatic cells cancer, agingIf it occurs in somatic cells cancer, aging If it occurs in germ cells teratogenecity.If it occurs in germ cells teratogenecity.

DNA functionsDNA functions 1- Replication1- Replication : : from one generation to another from one generation to another

inheritance.inheritance. From cell to cell division.From cell to cell division. 2-Metabolism:2-Metabolism: Gene expression& protein synthesisGene expression& protein synthesis (transcription& translation).(transcription& translation).

DNA replicationDNA replication It is the process by which genetic information is It is the process by which genetic information is

transmitted from one cell to another.transmitted from one cell to another. It starts by separation of the 2 strands. Each It starts by separation of the 2 strands. Each

acts as a template for a new strand.acts as a template for a new strand. (semi-conservative).(semi-conservative). DNA polymerase proceeds in only one direction DNA polymerase proceeds in only one direction

along the helix along the helix (from the 5’ to 3’ end of (from the 5’ to 3’ end of DNA)DNA) but starts in many sites. It is continuous in but starts in many sites. It is continuous in one strand and discontinuous in the other.one strand and discontinuous in the other.

Enzymes for DNA replicationEnzymes for DNA replication 1-Gyrase:1-Gyrase: prevents supercoil formation. prevents supercoil formation. 2-Helicase:2-Helicase: local unwinding. local unwinding. 3-Primase:3-Primase: synthesis of RNA primers. synthesis of RNA primers. 4-Polymerase4-Polymerase: base pairing.: base pairing. 5-Ligase:5-Ligase: ligates the newly synthesized ligates the newly synthesized

fragments together.fragments together.

DNA replicationDNA replication

Transcription Transcription TranscriptionTranscription : : the process whereby genetic information is the process whereby genetic information is

transmitted from DNA to m.RNA by RNA transmitted from DNA to m.RNA by RNA polymerase into complementary single-polymerase into complementary single-stranded copies of RNA.stranded copies of RNA.

m.RNA m.RNA are the processed transcripts of are the processed transcripts of genes that code for polypeptides.genes that code for polypeptides.

ExonsExons : the transcribed parts of DNA.: the transcribed parts of DNA. IntronsIntrons : non-translated parts of DNA. The : non-translated parts of DNA. The

function is unknown. Although transcribed, function is unknown. Although transcribed, they are later cut during RNA processing. they are later cut during RNA processing.

>80% of DNA does not code for proteins >80% of DNA does not code for proteins (repetitive {r.RNA+t.RNA}, around (repetitive {r.RNA+t.RNA}, around centromeres, introns).centromeres, introns).

Promoter:Promoter: the place where RNA the place where RNA polymerase 1polymerase 1stst attaches. They vary from attaches. They vary from gene to another but contain sequences in gene to another but contain sequences in common of 7 base sequence of all T’s&A’s common of 7 base sequence of all T’s&A’s (TATA box, upstream before the 3’ end).(TATA box, upstream before the 3’ end).

Termination:Termination: certain sequence that certain sequence that terminates gene transcription (downstream terminates gene transcription (downstream beyond the 5’ end).beyond the 5’ end).

Sense strandSense strand The strand that is actually transcribed is The strand that is actually transcribed is

the one with specific promoter sequence. the one with specific promoter sequence. The other non-sense strand is not used in The other non-sense strand is not used in transcription.transcription.

The sense strand at one place may not The sense strand at one place may not make sense elsewhere in a chromosome.make sense elsewhere in a chromosome.

The SS of one gene may be continuous The SS of one gene may be continuous with the anti-sense of another.with the anti-sense of another.

Steps of transcriptionSteps of transcription 1-Local unwinding (DNA helicase).1-Local unwinding (DNA helicase). 2- Base pairing (DNA polymerase).2- Base pairing (DNA polymerase). 3-Separation of mRNA.3-Separation of mRNA. Processing:Processing: A) A) capping:capping: addition of a chemical cap to the 5’ addition of a chemical cap to the 5’

end( attach RNA to the ribosome)end( attach RNA to the ribosome) B) B) splicing:splicing: excision of introns. excision of introns. C) C) polytail:polytail: addition of poly A tail (AAAA) to the addition of poly A tail (AAAA) to the

3’ end( it aids in transporting RNA molecule into 3’ end( it aids in transporting RNA molecule into the cytoplasm)the cytoplasm)

TranscriptionTranscription

TranslationTranslation It is the process by which m.RNA is It is the process by which m.RNA is

translated into protein synthesis. It translated into protein synthesis. It involves t.RNA & r.RNA.involves t.RNA & r.RNA.

t.RNA:t.RNA: one end binds a particular aa (all one end binds a particular aa (all are 20), the other end has a 3-base are 20), the other end has a 3-base sequence, the anticodon, that pairs with a sequence, the anticodon, that pairs with a particular codon on m.RNA.particular codon on m.RNA.

r.RNA:r.RNA: structural elements of ribosomes. structural elements of ribosomes. They are the benches on which protein They are the benches on which protein synthesis occurs. synthesis occurs.

Steps of translationSteps of translation 1-mRNA moves along ribosomes1-mRNA moves along ribosomes 2-tRNA adapts2-tRNA adapts 3-Starting codon= 3-Starting codon= AUGAUG 4-Stop codon= 4-Stop codon= UGA, UAG, UAAUGA, UAG, UAA DNA transcription at chromosomes DNA transcription at chromosomes

RNAs movement across NM RNAs movement across NM RNAsRNAs

translation at ribosomes protein translation at ribosomes protein

Translation Translation